It is known that α-tocotrienol quinones are pharmaceutically active.
US 2011/0172312 A1 discloses that tocotrienol quinones are used in treating Leight Syndrome. WO 2010/126909 A1 and US 2006/0281809 A1 disclose that tocotrienol quinones can be used for treating ophthalmic diseases and mitochondrial diseases. U.S. Pat. No. 5,318,993 discloses the activity of tocotrienol quinones as cholesterol suppression. W. D. Shrader et al., Bioorganic & Medical Chemistry Letters 21 (2011), 3693-3698 disclose that the R-isomer of α-tocotrienol quinone is a metabolite of α-tocotrienol and is a potent cellular protectant against oxidative stress and ageing. The R-isomer of α-tocotrienol used for this study has been extracted from Elaeis guineensis. All these documents either use tocotrienol from natural sources or do not disclose the source of tocotrienol respectively tocotrienol quinones or disclose very specific complex synthesis thereof. These methods are very expensive and limited in producing industrial amounts of the desired products.
It is well known that from vitamin E the tocopherols and tocotrienols having the R-configuration have a significantly higher bioactivity (biopotency) than the corresponding S-isomer. This is also the case for the corresponding R-isomers of tocotrienol quinones.
Synthetic pathways to produce the R-isomer of tocotrienol quinones in a stereospecific way are very expensive and therefore only of limited interest. The synthesis of α-tocotrienol is known from Kabbe and Heitzer, Synthesis 1978, 888-889, however, no indication of chirality whatsoever is indicated.
The synthesis of tocotrienol from the corresponding 4-oxo-chromanol-derivative is known from U.S. Pat. No. 6,096,907, however, no indication of chirality is indicated.
J. Org. Chem. 1981, 46, 2445-2450 and CH 356754 disclose the chemical transformation of α-tocopherol to α-tocopheryl quinone and to α-tocopherylhydro-quinone, however, neither tocotrienols nor tocotrienol quinones are mentioned.
Separation of chiral compounds by chromatography is principally known. However, it is also known that the quantitative separation is very often very difficult to achieve.
Due to the importance of these substances, there exists a high interest in a process which would produce R-tocotrienol quinones in a large scale in an easy and economic way.